Lung cancer is the leading cause of cancer death in the United States, and it is estimated that 171,900 new cases will be diagnosed in 2003. It is estimated that 157,200 of these patients will ultimately die from their lung cancer, primarily because they will have advanced stage disease at the time of diagnosis. The burden of lung cancer is not shouldered exclusively by people who continue to smoke cigarettes. While 40-50 million Americans have stopped smoking, their risk of developing lung cancer remains high for as many as 30 years after smoking cessation. Vitamin D [1,25 dihydroxycholecalciferol (calcitriol)] is a potent anti-proliferative agent in a variety of malignant cell types, including human squamous cell carcinoma (SCC) and human xenograft lung cancer. The chemopreventive activity of calcitriol in modulating expression of markers of tissue damage, including proliferation (MCM2), disruption of apoptotic pathways (Bcl-2), the epidermal growth factor receptor (EGFR), AKT and will be evaluated. For this study, high-risk former smokers with premalignant lesions (squamous metaplasia or dysplasia) documented by autofluorescence (AF) bronchoscopy will be recruited as subjects in the Phase II study. We propose to examine the potential chemoprevention effect of calcitriol for inhibiting the progression of dysplasia and metaplasia, and for the prevention of new premalignant lesions detectable with AF bronchoscopy, and for altering biomarkers expression, using a 6-month incomplete crossover design that will randomize subjects to either a placebo or 16 meg of calcitriol for 3 days per week. Serial AF bronchoscopies at 6 and 12 months after randomization will demonstrate the efficacy of this potential chemopreventive agent for progression premalignant bronchial epithelial lesions. The Primary Hypothesis for this study is that calcitriol will prevent the progression of metaplastic or dysplastic lesions at specific sites in the bronchial epithelium and will inhibit the formation of new dysplastic or metaplastic lesions throughout the lung field. The secondary hypotheses is that calcitriol will alter biomarkers of apoptosis and growth signaling in the bronchial epithelium, and that calcitriol supplementation three days per week will show an acceptable toxicity profile.